title: Treatment of BRAF-mutant melanoma: the role of vemurafenib and other therapies.
abstract: The discovery of activating BRAF mutations in melanomas has led to the investigation of small molecular inhibitors targeting BRAF mutation and MEK, a downstream protein within the mitogen-activated protein kinase (MAPK) pathway. This article reviews the role of mutant BRAF in melanoma and summarizes the results of clinical trials evaluating inhibitors of BRAF and MEK in BRAF-mutant melanoma. We further describe recent findings on the mechanisms of resistance to BRAF inhibitors and discuss ongoing efforts to combine BRAF inhibitors with other targeted agents. Finally, we review the results of immunotherapy in BRAF-mutant melanoma and address the current status of efforts to either combine or determine the optimal sequence of these two distinct treatment approaches. Although the recent advances in melanoma therapy have been dramatic, greater understanding of melanoma biology coupled with the successful development of several new treatments and combination regimens will further improve patient outcomes in the future.
authors.affiliation: 1] Department of Medicine, Georgetown University School of Medicine, Washington, DC, USA [2] Hematology and Oncology, MedStar Washington Hospital Center, Washington, DC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Jang
authors.affiliation: 1] Division of Hematology and Oncology, Georgetown University School of Medicine, Washington, DC, USA [2] Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Atkins
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf